The proposed research addresses the question of whether growth in normal and neoplastically transformed mammalian cells in culture is controlled by alterations in specific membrane transport of metabolites, particularly nucleic acid precursors. Purified plasma membrane vesicles capable of concentrative uptake of purines, pyrimidines and nucleosides will be employed in order to isolate the biochemical mechanisms involved in transport from other cellular activities which influence uptake. Each vesicle transport system will be characterized with regard to its kinetics, mechanism, regulation, and lipid and energy requirements. Such characterizations will also include the effects on transport of, limited proteolysis, binding of plant lectins and binding of antibody to surface membrane localized histocompatibility determinants. The plasma membrane vesicles will be subfractionated into several populations using density gradients and affinity chromatography in order to determine the mosaicism of surface membrane with regard to transport function. Characterized and subfractionated vesicles will then be used to determine differences in transport systems from vesicles derived from cells as follows: 1) Confluent versus non-confluent growth in a contact inhibited cell-line. 2) Normal parental cell line versus its SV40 transformed derivative. 3) Contact inhibited versus serum reversed state. 4) Discrete cell cycle stages in synchronous cell populations. In addition, transport into vesicles prepared from internal membranes of the cells, into isolated nuclei, and into enucleated cells, will be studied in order to gain perspective in the overall regulatory processes in nucleic acid precursor utilization and the involvement of each cell compartment.